O.A., Aguilar A., Mesci J., Ma P., Chen C.L., Kirkham J., Hundrieser S., Voigt D.S.J., Allan J.R., Carlyle Supplementary Material for: Modulation of Clr Ligand Expression and NKR-P1 Receptor Function during Murine Cytomegalovirus Infection Viruses are known to induce pathological cellular states that render infected cells susceptible or resistant to immune recognition. Here, we characterize an MHC-I-independent natural killer (NK) cell recognition mechanism that involves modulation of inhibitory NKR-P1B:Clr-b receptor-ligand interactions in response to mouse cytomegalovirus (MCMV) infection. We demonstrate that mouse Clr-b expression on healthy cells is rapidly lost at the cell surface and transcript levels in a time- and dose-dependent manner upon MCMV infection. In addition, cross-species infections using rat cytomegalovirus (RCMV) infection of mouse fibroblasts and MCMV infection of rat fibroblasts suggest that this response is conserved during host-pathogen interactions. Active viral infection appears to be necessary for Clr-b loss, as cellular stimulation using UV-inactivated whole virus or agonists of many innate pattern recognition receptors failed to elicit efficient Clr-b downregulation. Notably, Clr-b loss could be partially blocked by titrated cycloheximide treatment, suggesting that early viral or nascent host proteins are required for Clr-b downregulation. Interestingly, reporter cell assays suggest that MCMV may encode a novel Clr-b-independent immunoevasin that functionally engages the NKR-P1B receptor. Together, these data suggest that Clr-b modulation is a conserved innate host cell response to virus infection that is subverted by multiple CMV immune evasion strategies. Natural killer cell;Mouse cytomegalovirus;MCMV;Nkrp1:Clr;Missing-self recognition;Host response 2015-05-29
    https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Modulation_of_Clr_Ligand_Expression_and_NKR-P1_Receptor_Function_during_Murine_Cytomegalovirus_Infection/5127985
10.6084/m9.figshare.5127985.v1